CAREER: Illuminating Emergent Microbial Interactions via Modular Synthetic Consortia

职业：通过模块化合成联盟阐明新兴微生物相互作用

• 批准号: 1845463
• 负责人: Daniel Ducat
• 金额: $ 103.4万
• 依托单位: Michigan State University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-05-01 至 2025-04-30
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1845463&HistoricalAwards=false
• 关键词: CAREER; Illuminating; Emergent; Microbial; Interactions

Microbial communities contribute important functions towards human health and biotechnology. Two examples are the many microbes associated with the human body (e.g., gut microbiome) and species that contribute to soil fertility and plant health. These natural microbial consortia that contain many different species, are often composed of poorly-characterized microbes. They also have complicated signaling networks of compounds and metabolites that are exchanged between community members. The complexity of natural consortia makes them difficult to study and can obscure identification of common principles that underlie many different communities. Consequently, many fundamental questions remain about how microbial consortia are organized to maintain productivity and resilience in the face of dynamic environmental conditions. This project makes use of artificial microbial communities that are relatively simple and composed of well-characterized microbes. These features of the artificial communities are chosen to facilitate an investigation that would lead to insight into underlying principles that guide the structure and function of microbial communities. The research activities increase knowledge of interaction dynamics in microbial communities, potentially improving the ability to engineer microbial consortia. The research also provides insight into the evolution of natural microbial symbioses. Through this project two graduate students and one postdoctoral fellow are trained. In addition, there are multiple undergraduate research experience opportunities. The project also involves promoting the development of public forums for the discussion of potential benefits and ethical concerns of bioengineering. These forums are hosted in the Michigan Science Center in Detroit.The research team is using a cyanobacterium (Synechococcus elongatus PCC 7942) that produces and secretes large quantities of sucrose from light and CO2. The PI has demonstrated that a variety of other microbes can be cultivated in the same media in a "modular" fashion. In these circumstances the co-cultured partner consumes the sucrose produced by the cyanobacteria. The flexibility in the design of these artificial microbial communities allows different heterotrophic bacteria to be cultivated with the cyanobacterium. In this way, common themes and mechanisms of interaction between the co-cultured species are identified. Approaches that include rational engineering, forward genetics, directed evolution, metabolic modeling, and individual-based simulations are used to identify the metabolites and signals exchanged between species. These approaches are also used to determine how metabolite exchanges contribute to consortia robustness. The knowledge gained is used to rationally design microbial communities that are more robust in the face of environmental pressures, such as invasion by "non-cooperating" microbial species. It is anticipated that the research efforts from this proposal will provide insights into fundamental interactions underpinning natural microbial symbioses, with translational impacts for the development of environmentally-sustainable cyanobacterial biotechnologies.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

微生物群落对人类健康和生物技术发挥着重要作用。两个例子是与人体相关的许多微生物（例如肠道微生物组）和有助于土壤肥力和植物健康的物种。这些天然微生物群落包含许多不同的物种，通常由特征不明确的微生物组成。它们还具有在群落成员之间交换的复杂的化合物和代谢物信号网络。自然群落的复杂性使得它们难以研究，并且可能模糊对许多不同群落背后的共同原则的识别。因此，关于微生物群落如何组织以在面对动态环境条件时保持生产力和恢复力，仍然存在许多基本问题。该项目利用相对简单且由特征明确的微生物组成的人工微生物群落。选择人工群落的这些特征是为了促进调查，从而深入了解指导微生物群落结构和功能的基本原理。这些研究活动增加了对微生物群落相互作用动力学的了解，有可能提高设计微生物群落的能力。该研究还提供了对自然微生物共生体进化的见解。通过该项目培训了两名研究生和一名博士后。此外，还有多个本科生研究经验机会。该项目还涉及促进公共论坛的发展，以讨论生物工程的潜在好处和伦理问题。这些论坛在底特律的密歇根科学中心举办。研究小组使用蓝细菌（细长聚球藻 PCC 7942），利用光和二氧化碳产生并分泌大量蔗糖。 PI 已经证明，可以以“模块化”方式在同一培养基中培养多种其他微生物。在这些情况下，共培养的伙伴消耗蓝藻产生的蔗糖。这些人工微生物群落设计的灵活性允许使用蓝藻培养不同的异养细菌。通过这种方式，可以确定共培养物种之间的共同主题和相互作用机制。包括理性工程、正向遗传学、定向进化、代谢建模和基于个体的模拟在内的方法用于识别物种之间交换的代谢物和信号。这些方法还用于确定代谢物交换如何促进联盟的稳健性。所获得的知识用于合理设计微生物群落，使其在面对环境压力（例如“不合作”微生物物种的入侵）时更加稳健。预计该提案的研究工作将深入了解支撑自然微生物共生的基本相互作用，并对环境可持续的蓝藻生物技术的发展产生转化影响。该奖项反映了 NSF 的法定使命，并通过使用基金会的智力价值和更广泛的影响审查标准进行评估，被认为值得支持。

项目成果

Investigating Carboxysome Morphology Dynamics with a Rotationally Invariant Variational Autoencoder

• DOI: 10.1021/acs.jpca.2c02179
• 发表时间: 2022-07-26
• 期刊: JOURNAL OF PHYSICAL CHEMISTRY A
• 影响因子: 2.9
• 作者: Fuentes-Cabrera, Miguel;Sakkos, Jonathan K.;Ziatdinov, Maxim
• 通讯作者: Ziatdinov, Maxim

Rubisco regulation in response to altered carbon status in the cyanobacterium Synechococcus elongatus PCC 7942

Rubisco 调节响应蓝细菌细长聚球藻 PCC 7942 中碳状态的改变

• DOI: 10.1093/plphys/kiac065
• 发表时间: 2022
• 期刊: Plant Physiology
• 影响因子: 7.4
• 作者: Singh, Amit K.;Santos-Merino, María;Sakkos, Jonathan K.;Walker, Berkley J.;Ducat, Daniel C.
• 通讯作者: Ducat, Daniel C.